SITE VALIDATION MASTER PLANRELEASING ITS FULL POTENTIAL

ASQ Definitions- Assurance: The act of giving confidence, the state of being certain or the act of making certain.

Quality assurance: The planned and systematic activities implemented in a quality system so that quality requirements for a product or service will be fulfilled.

FDA Definition- Validation: Establishing documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications.

Validation Master Plan The companys overall policy, intentions and approach to validation, including the validation of production processes, cleaning methods, analytical test methods and computerized systems, should be established in the Validation Master Plan.

Site Validation Master Plan versus:

Project Master Plan Cleaning Validation Master Plan Process Validation Master Plan Computer System Validation Master Plan

Site Validation Master PlanWhat PurposeWhere Scope Why Policy & RationaleWho ResponsibilitiesHow Doc. Content & FormatWhen Prioritization & Sched.

Site Validation Master Plan- Scope

FacilitiesLab EquipmentLaboratory MethodsWater & SteamHVACGas SystemsMfg. EquipmentProcessCleaningComputer Systems

Equipment QualificationGeneralPre-Qualification ActivitiesQualification ActivitiesProtocol PreparationInstallation, Operational & Performance QualificationAcceptance CriteriaSummary ReportRe-qualification

Exclusions Employs commonly used technology. Is easily installed. Is routinely (minimum daily) checked for accuracy prior to use.Does not require specialized operating skills and expertise.Test instrumentation and simple equipment (pH meters, viscometers, scales) will be qualified via a procedure instead of a protocol. The procedure approach is applicable to equipment that:

Re-qualification The definition of what constitutes a change to lab equipment that may require re-qualification includes the following: Failure of test results Relocation- equipment unplugged and moved within a room, between rooms, between buildingsMajor component changes or modifications, including software changes

Planning Step # 1: Inventory Existing WorkEquipment List & Schedule:

Product Contact List

FDA 483 ObservationsNot all manufacturing ISO Class [removed] rooms, Biological Safety Cabinets and manufacturing equipment have documentation of cleaning validations.No validation studies were conducted to support cleaning of the [removed].

Product/Equipment Matrix

Planning Step # 2: PrioritizationPriority 1 Products:

Planning Steps 3 & 4:Establish a Timeline & Estimate Resources

SITE VALIDATION MASTER PLAN

2009

.Gas6 mo.MENSZAK2Q 20082010

2015

2012

2011

HVAC & LFUs2.0 yrs.Lab Equip. Qual. 1.5 yrs.All Other Process Validation 5.0 yrs.

Cleaning Methods yr.All Other Equipment 2.0 yrs.20172013

2014

2016

LOC Transfer ProjectAll Other ValidationAll Other Cleaning Validation4.25 yrs.

LOC Equipment 1.5 yrs.LOC Process Validation3.0 yrs.Total Process Validation 8.0 yrs.LOC Cleaning Validation3.75 yrs.

Total Cleaning Validation8.0 yrs.

LOC Methods Validation3.0 yrs.Total Methods Validation9.0 yrs.All Other Methods6.0 yrs.Total Equipment Qualification 3.5 yrs.

Site Validation Master Plan ValueThe Site Validation Master Plan provides clarity, and it enables the validation manager to communicate the workload, capacity constraints and justify the need for resources. It facilitates effective management and the best performance.

Planning Step # 6: Repeat Steps 1-5 The firm has a protocol for the qualification of solutions used in Manufacturing. This protocol has been effective since 21 Dec 2004. To date only 2 of the approximately 50 materials used in either the manufacture of products or for cleaning/disinfection have been qualified.FDA 483 Observation:

Six Steps to Planning:

Inventory all existing and upcoming work.Prioritize.Establish a timeline.Estimate the resources needed.Communicate to upper management for involvement, commitment and resources.Repeat Steps 1-5 on a routine basis.

Process OptimizationHow?

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1. Identify the TaskDocument ChangesProtocol Approval(Signed)Protocol Execution(Signed)Summary Report Approval (Signed)DraftRevisionAmendmentAddendum

2. Concentrate the Work

3. Form Partnerships

4. Define PerformanceResponsibilities Matrix:

5. TrainingThe greatest benefit of training comes not from learning something new, but from doing better what we already know.

Five Steps to OptimizationIdentify the tasks.Concentrate the work.Define performance.Form partnerships. Build continuous learning and teaching.

Constraints vs. PerformanceQualityCostTimeScope

Look at the Big PicturePeriodic review applying an holistic approach to quality systems.

Process OptimizationIncorporate steps to optimize individual processes (quality system).Look at the constraints.Periodically review applying an holistic approach to quality systems.

Why? Regulatory Requirement Assures Quality Good Economics

ReferencesASTM E 2500-07 Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and EquipmentICH Q9 Quality Risk HandbookPharmaceutical cGMPs for the 21st CenturyA Risk-Based ApproachFDA Guide to Inspections of Quality Systems- August 1999The Gold Sheet- January 2008: Quality Systems No Longer Theoretical as Industry Begins Implementing Concepts

Lee Menszak Consulting, Inc.leeminc@earthlink.net 845-300-1730

Basic principles of QA: 1) Quality, safety, effectiveness. 2) Cannot inspect quality into a product. 3) Processes must be under control.The term VMP, when used by device manufacturers is often in the context of a specific product or process. For example, Product Development Protocols require the submission of a VMP. Although FDA is explicit about the need for validation, it remains implicit about the VMP and its content. Demonstrates corporate commitment, it is a resource, it answers inspectors questions, it helps personnel at all levels of management understand how validation is approached. Assumptions, Exclusions, Limitations, & Risk Assessment

Key metrics for measuring the value needs to be hard and quantifiable--increased efficiency, lower cost, improved return on investment

Key metrics for measuring the value needs to be hard and quantifiable--increased efficiency, lower cost, improved return on investmentDelegate upMore than a document approval matrix. Provide input, deliverables, or determine priorities. Write or delegate responsibilities. Execute. Approve, Concur, or Optional